Theoretically, single patient room newborn intensive care units are designed to optimize the developmental outcomes of critically ill infants by providing individual patient environments with decreased stimulation and noise. This article reports the perceptions of 127 neonatal intensive care nurses after the move into a single room neonatal intensive care unit (NICU). The observations of the nurses were obtained using a questionnaire to identify some of the benefits, risks, and specific patient safety concerns related to the single room NICU design. The results suggest that in this setting the single patient room concept was deemed superior for patient care and parent satisfaction when compared to the large open unit. However, the nurses emphasize that the success of single room care model primarily depends on providing sufficient staff coverage, given the decreased patient visibility and greater distances between patients. Larger units also present unique communication, staff education, and quality improvement challenges. To further evaluate the impact of single room designs we evaluated data on important clinical issues, specifically noise levels and catheter-related infections provide objective measures of important improvements. Noise levels decreased from an average of 63 to 56 decibels and catheter-associated bloodstream infections fell from 10.1 per 1000 device days to 3.3 per 1000 device days in the 9 months after the move to single patient rooms. This article provides pragmatic design suggestions that should be prospectively considered to minimize staff isolation and stress.